P1414: CRP IS A CONVENIENT PREDICTIVE MARKER OF THE ANTIPYRETIC EFFECT OF TOCILIZUMAB ON CRS DURING CAR-T CELL THERAPY
Authors: Shota Yokoyama, Takahide Ara, Shinpei Harada, Yuto Mori, Yuta Hasegawa, Hiroyuki Ohigashi, Toshihiro Matsukawa, Atsushi Yasumoto, Souichi Shiratori, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Hideki Goto, Takanori Teshima
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Cytokine release syndrome (CRS) is an important adverse event in chimeric antigen receptor (CAR)-T cell therapy. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is used for CRS. Furthermore, corticosteroids are used when TCZ is refractory to CRS. Predicting response to these drugs is clinically important because patients with severe CRS may admit to ICU. IL-6 is essential for the synthesis of acute phase proteins such as C-reactive protein (CRP), and elevated CRP is considered a state of increased IL-6 production. In addition, measurement of CRP is easy even in daily clinical practice. Recently studies reported that highly elevated CRP was associated with responsiveness to TCZ in rheumatoid arthritis patients. However, the clinical significance of CRP in patients receiving CAR-T cell therapy was still unknown. Aims: To validate the usefulness of CRP as a biomarker of the antipyretic effect of TCZ on CRS in CAR-T cell therapy. Methods: A total of 35 (DLBCL=34, ALL=1) patients received CAR-T cell therapy (Tisa-cel=33, Axi-cel=1, Liso-cel=1) from October 2019 to December 2022 at Hokkaido University Hospital. We retrospectively analyzed 25 patients, excluding patients without CRS (n=4), with CRS but not used TCZ (n=6), and complicated with infection (n=3). We assessed peak CRP from the onset of CRS to within 2 days after the first TCZ use. The antipyretic effect of TCZ was evaluated by mean body temperature (mean BT) during the 24 hours before and after first TCZ use. To assess the ability of CRP to predict the antipyretic effect of TCZ, we performed a receiver operating characteristics (ROC) curve analysis and calculated the positive and negative predictive values. Results: We obtained cutoff values of peak CRP 8.97 (mg/dL). Using these cutoff values, patients were classified as high CRP group (n=9) and low CRP group (n=13). Characteristics, CRS details, and ICANS detail of both groups are summarized in Table 1. Although little difference in the characteristics of the two groups, LDH was significantly higher in high CRP group. The onset from CAR-T cell infusion, the number of TCZ use, and the duration from CRS to TCZ use were not significantly different in two groups. Grade ≥3 CRSs were observed more frequently in high CRP group, but ICANS were only observed in low CRP group. Eight patients (53.8%) in low CRP group received corticosteroids for fever, but all three patients (33.3%) in high CRP group received corticosteroids for reasons other than fever. Finally, we compared the antipyretic effect of first TCZ use between both groups. The percentage of patients with mean BT reduction after the first TCZ use was significantly higher in the high CRP group than in the low CRP group (77.8% vs 23.1%, P= 0.00732). Interestingly, regarding the change in mean BT before and after the first TCZ use, high CRP group decreased BT by 0.5 degree Celsius (range, 0 to 1.2), while low CRP group increased 0.1 degree Celsius (range, -0.7 to 0.6) (P=0.00436).Summary/Conclusion: Antipyretic effect by TCZ use was not in low CRP group, and many patients in low CRP group required treatment with corticosteroids. This result shows that CRP may be a biomarker for the antipyretic effect of TCZ in CRS. A larger prospective study is desirable. Keywords: CAR-T, Cytokine release syndrome, ALL, DLBCL